Abstract

2162

The antibody AR7BD-33-11A was created through a non-standard approach for the generation of functional anti-cancer antibodies based on whole cancer cell immunization, followed by screening specifically for differential, anti-cancer function. AR7BD-33-11A, as a naked antibody, has the capacity to kill breast and prostate cancer cells in vitro, with no effect on non-cancer cells. This antibody is significantly more effective in suppressing tumor growth in both preventative and established heterotopic SCID mouse xenograft models of human breast and prostate cancers compared to an isotype control antibody. This antibody is highly potent; significant inhibition of breast cancer tumor growth is obtained at weekly doses of only 0.2 mg/mL. Immunohistochemistry (IHC) studies were carried out in normal and cancerous human tissue sections to demonstrate that the target of AR7BD-33-11A is a relevant cancer antigen in humans. In all positive cases, the antibody displayed both membrane and cytoplasmic staining patterns. The majority of normal human tissues failed to express the AR7BD-33-11A antigen, including the vital organs, such as the kidney, heart, and lung. In a survey of tissue samples from 50 individual breast cancer patients, 36 percent of tissue samples stained positively for the AR7BD-33-11A antigen. Expression of AR7BD-33-11A within patient samples appeared specific for cancer cells as staining was restricted to malignant cells. In addition, AR7BD-33-11A stained none of the normal tissues from breast cancer patients in ten cases. Several cancer types, other than breast cancer, also expressed the AR7BD-33-11A antigen. These included cancers of the skin (1/2), lung (3/4), liver (2/3), stomach (4/5), thyroid (2/2), prostate (1/1), uterus (4/4) and kidney (3/3). Those that did not express the antigen included cancers of the ovary (0/3), testis (0/1), brain (0/2) and lymph node (0/2). These results demonstrate that the AR7BD-33-11A antigen is a cancer-associated antigen which is expressed in humans, and is a pathologically relevant cancer target. AR7BD-33-11A is a potent and functional antibody recognizing this target, with demonstrated therapeutic effects in breast and prostate cancer.